Abdominal aortic aneurysm (AAA) is a common disease in the elderly and an important public health problem. Ruptured AAA is associated with a 65% to 85% mortality rate and ranked one of the leading causes of death in the elderly. Elective surgery or endovascular repair for identified large AAA are the only effective interventions for AAA and there are no specific pharmacological agents that have been shown to be effective in preventing or reducing AAA progression in the general population. The etiology of AAA is complex and not well understood. Although traditional cardiovascular risk factors have been associated with the risk of AAA, their importance in the etiology of AAA is not well established. Furthermore, the novel etiopathogenic mechanisms such as extracellular matrix remodeling and degradation, inflammation, and thrombosis have been hypothesized but their roles are not appropriately determined. We propose to take advantage of the planned cardiac ultrasound exams in the Atherosclerosis Risk in Communities (ARIC) Study to perform an ultrasound examination of the abdominal aorta to identify undiagnosed AAA cases in this large population-based cohort. In addition, these will be pooled with 265 existing cases already identified through hospital records and those to be identified through Medicare linkage. Utilizing the risk factor and plasma samples already collected in ARIC at baseline, we will conduct epidemiological studies of AAA in this large prospective cohort that has been followed for more than 20 years. The specific aims of this application are: 1) to perform an ultrasound examination of the abdominal aorta in approximately 6,886 ARIC participants, 25% African-Americans, who will be 67-89 years and expected to attend the next ARIC exam in 2011-13. Based on a prevalence estimate of 6.1% asymptomatic AAA in men and 1.7% in women older than 65 years, we anticipate to identify 235 undiagnosed AAA cases in the ARIC cohort. With the previously diagnosed clinical cases during 1987-2011, we expect a total of 475 AAAs. 2) To investigate the associations of AAA with potential novel risk factors previously measured in ARIC or to be measured in stored blood samples collected at ARIC baseline in 1987- 89. Specifically, we will evaluate novel biomarkers in the following categories: (a) extracellular matrix remodeling; (b) extracellular matrix degradation; (c) inflammation; and (d) thrombosis. This study will be the first to comprehensively evaluate the role of novel risk factors in the etiology of AAA in a large, population- based cohort of middle-aged adults followed for more than 20 years. Conducting this study within ARIC takes advantage of ARIC's extensively characterized cohort, existing biological samples available at no cost to the current project, and provides a particularly rapid and cost-effective way to establish an AAA cohort as the abdominal ultrasound protocol is readily added to the cardiac ultrasound to be performed in the 2011-13 ARIC exam. PUBLIC HEALTH RELEVANCE: Data from this study will provide new insights in the biological determinants of AAA, and potentially improve prevention and early management of AAA to prevent ruptures.